We have shown that the transmural distribution of myocardial flow is often abnormal in awake dogs with left ventricular hypertrophy. In addition, studies of two animal models of cardiac hypertrophy (pressure and volume-induced hypertrophy) in our laboratory have shown that maximal coronary vasodilatation is limited substantially. Many additional studies are needed in this area. First, factors that modify the response of the coronary circulation to cardiac hypertrophy need to be explored. The duration that the hypertrophy has been present and the magnitude of the hypertrophy may be important determinants. Second, effects of cardiac hypertrophy on critical closing pressure in the coronary circulation need to be examined for total flow and in various layers of the myocardium. Vascular hypertrophy which occurs in coronary resistance vessels in dogs with left ventricular hypertrophy secondary to hypertension and postulated alterations in the transmural distribution of wall stress in left ventricular hypertrophy could significantly increase critical closing pressure. Third, since cardiac hypertrophy decreases the vascular capacity of the coronary circulation, it will be important to determine whether or not this abnormality is altered if the hypertrophy regresses. Fourth, it will be important to assess the effects of cardiac hypertrophy and failure on the coronary reserve in man. The recent development in my laboratory of a method measuring phasic coronary velocity and reactive hyperemia (an excellent measure of coronary reserve) in man should permit such studies to be accomplished. In preliminary studies, we have shown that the method is safe, and we have defined the quantitative characteristics of coronary reactive hyperemia in normal man. In addition, preliminary studies have shown that coronary reactive hyperemia is profoundly decreased in patients with normal coronary arteries and left ventricular hypertrophy secondary to aortic stenosis. The decrease in coronary reserve may in part be responsible for the gradual functional deterioration that occurs in hypertrophied ventricles and may explain some of the clinical features of the illness such as angina pectoris and subendocardial fibrosis.